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A polymerase chain reaction study of the stability of Ig heavy-chain and
T-cell receptor delta gene rearrangements between presentation and relapse
of childhood B-lineage acute lymphoblastic leukemia
CG Steward, NJ Goulden, F Katz, D Baines, PG Martin, K Langlands, MN Potter, JM Chessells and A Oakhill
Department of Pathology, Bristol University Medical School, UK.
Ig heavy-chain (IgH) and partial V delta 2-D delta 3 T-cell receptor (TCR)
gene rearrangements were investigated, by polymerase chain reaction (PCR)
amplification and sequence analysis, in 52 patients at presentation and
first relapse and in 14 at both first and second relapse of B-lineage acute
lymphoblastic leukemia. In combination, these techniques amplified one or
more clonal markers at presentation in 90% of patients (IgH-PCR, 75%; V
delta 2-D delta 3-PCR, 46%; both, 33%). Changes in the pattern of
amplification between presentation and first relapse were seen in 31% of
patients positive by IgH-PCR at presentation and in 25% of those positive
by TCR delta-PCR. Only 3 patients showed complete change in their
rearrangements, which is suggestive of relapse with a new clone.
Furthermore, despite the high reported rates of oligoclonality and clonal
evolution at the IgH locus, the results presented show that false-negative
minimal residual disease (MRD) detection can be avoided by designing D-N-J
probes to all presentation rearrangements. Using a PCR approach for both
gene markers, false-negative testing because of clonal evolution would have
only occurred in 3 (8%) of the IgH-positive patients, in contrast to 5
(21%) of V delta 2-D delta 3-positive patients. Combining these two systems
increases the proportion of patients open to study to 90%, allows
comparative studies of the sensitive of the two methods, and reduces the
rate of false-negative assessment of MRD caused by clonal evolution to less
than 10%. We conclude that large prospective PCR studies of MRD detection
should examine gene rearrangements at multiple loci to maximize their
applicability and to minimize false-negative relapse prediction.
Volume 83,
Issue 5,
pp. 1355-1362,
03/01/1994
Copyright © 1994 by The American Society of Hematology
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